European Journal of Medical Research最新文献

Background: The hypoxia-inducible factor-1α (HIF-1α)/Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3) pathway, a key regulator of mitophagy, has demonstrated protective effects in renal and cardiac ischemia/reperfusion (I/R) injury. However, its specific role and mechanism in cerebral I/R injury (CIRI) are not fully understood.

Methods: An oxygen-glucose deprivation/reoxygenation (OGD/R) model in SH-SY5Y neuroblastoma cells and a transient middle cerebral artery occlusion (MCAO) model in rats were established to simulate CIRI. HIF-1α overexpression plasmids was then introduced into the two models. Mitophagic activity was assessed through immunoblotting of BNIP3, microtubule-associated protein 1 light chain 3B (LC3B), and p62 protein, quantification of LC3B-mitochondria colocalization, and transmission electron microscopic analysis of mitochondrial ultrastructure and autophagosomes. NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome activation was evaluated by measuring levels of NLRP3, cleaved caspase-1, interleukin (IL)-1β, and IL-18. The cell-type specificity of the HIF-1α/BNIP3/mitophagy pathway was evaluated by comparative analysis in SH-SY5Y neuronal cells and BV-2 microglia. Mechanistic dependency was tested NLRP3 agonist nigericin using the autophagy inhibitor 3-methyladenine (3-MA) and the specific NLRP3 inflammasome agonist nigericin in rescue experiments. In addition, cerebral infarction and neurological deficits were assessed in rats.

Results: HIF-1α transcriptionally upregulated BNIP3 in SH-SY5Y cells. HIF-1α overexpression increased BNIP3 and LC3B II levels, reduced p62 level, increased autophagosome accumulation, and enhanced mitophagy in SH-SY5Y cells. This enhanced mitophagy suppressed OGD/R-induced apoptosis and NLRP3 inflammasome activation, while these effects were abolished by 3-MA or nigericin. Comparative analysis revealed the HIF-1α/BNIP3/mitophagy pathway to be a predominant and potent mechanism in SH-SY5Y cells, rather than BV-2 microglia. In addition, HIF-1α overexpression enhanced mitophagy and attenuated NLRP3 inflammasome activation in brain tissues, thereby alleviating cerebral infarction and neurological deficits in MCAO rats.

Conclusions: Activation of the HIF-1α/BNIP3 pathway drives protective mitophagy to suppress the NLRP3 inflammasome in neuronal cells, thereby conferring neuroprotection against CIRI. This study provides mechanistic insights into the protective role of HIF-1α/BNIP3-mediated mitophagy against CIRI, highlighting its potential as a therapeutic target for ischemic injury.

Background: The incidence of Mycobacterium avium complex (MAC)-pulmonary disease (PD) is increasing in South Korea, posing significant diagnostic and therapeutic challenges. Treatment guidelines recommend initiating therapy after serial computed tomography monitoring. Patients with the nodular bronchiectatic (NB) form often respond positively to drug therapy, whereas those with the fibrocavitary (FC) form frequently experience persistent disease despite treatment. Identifying phenotype-specific transcriptomic biomarkers could improve early diagnosis and inform personalized therapeutic strategies.

Methods: We utilized surgically resected lung specimens from 21 MAC-PD patients, a valuable clinical resource, as lung surgery is uncommon in MAC-PD management. Each patient provided paired samples of affected and unaffected lung tissues, enabling direct transcriptomic comparisons. Quantitative RNA sequencing was performed on samples from 11 NB and 10 FC cases. Comprehensive bioinformatics and in silico analyses, including gene ontology (GO) and protein-protein interaction (PPI) network analyses, were conducted to identify key diagnostic signatures and biological pathways.

Results: RNA sequencing revealed distinct and shared transcriptomic signatures correlated with radiological phenotypes. GO and PPI analyses identified significant gene clusters involved in B cell proliferation and immune regulation across both NB and FC forms. Additionally, NB-specific signatures highlighted genes predominantly regulating antimicrobial immune responses, while FC-specific signatures enriched genes related to extracellular matrix remodeling.

Conclusions: This study is the first to characterize transcriptomic differences between MAC-PD phenotypes using paired lung tissue samples. Although the identified transcriptomic markers require functional validation, their strong correlation with radiologic subtypes provides preliminary evidence supporting their potential diagnostic value. These findings lay the groundwork for precision diagnostics in MAC-PD and require further validation in larger patient cohorts and through functional assays.

Background: SGLT-2 inhibitors and GLP-1 receptor agonists exhibit metabolic benefits on improving obesity, diabetes, hypertension and hyperlipidemia, but the differences between them remain unclear. We evaluated the comparative efficacy of these two agents on metabolic benefits in adults with T2DM.

Method: This study has searched the electronic databases from the inception of the databases up to March 30, 2025. Primary outcome was the efficacy for weight loss. Secondary outcomes included the effectiveness for HbA_1c levels, blood pressure, and plasma lipid levels. We conducted a Bayesian network meta-analysis. This protocol was cataloged with PROSPERO (CRD42021247584).

Results: 168 RCTs of 72,195 adults were deemed eligible. For losing weight, GLP-1 receptor agonists were more effective than SGLT-2 inhibitors (MD - 1.08 kg,95% CrI: - 1.78 to -0.36). In subgroup analyses, compared to SGLT-2 inhibitors, GLP-1 receptor agonists displayed a stronger weight-loss effect in subgroup of 30 kg/m² ≤ BMI < 35 kg/m² (- 0.95 kg, - 1.91 to - 0.01) and BMI ≥ 35 kg/m² (- 1.11 kg, - 6.73 to - 4.60), while had a weaker weight-loss effect in subgroup of 25 kg/m² ≤ BMI < 30 kg/m² (1.33 kg, 0.79-1.83). For lowering plasma glucose, GLP-1 receptor agonists showed a stronger effect on reducing HbA_1c level (- 0.38%,- 0.52 to - 0.25). For decreasing blood pressure, both GLP-1 receptor agonists (- 2.10 mmHg, - 3.66 to - 0.49) and SGLT-2 inhibitors (- 3.20 mmHg, - 4.0 to - 2.39) decreased systolic blood pressure, while only SGLT-2 inhibitors (- 1.35 mmHg, - 1.67 to - 1.01) decreased diastolic blood pressure compared to placebo. For regulating serum lipids, both GLP-1 receptor agonists (- 0.14 mmol/L, - 0.22 to - 0.08) and SGLT-2 inhibitors (- 0.12 mmol/L, - 0.18 to - 0.07) lowered triglycerides, while only GLP-1 receptor agonists lowered LDL-c level (- 0.14 mmol/L, - 0.22 to - 0.06) compared to placebo.

Conclusion: Both GLP-1 receptor agonists and SGLT-2 inhibitors have been shown to confer metabolic benefits. GLP-1 receptor agonists displayed stronger effects on weight reduction for patients with obesity (BMI ≥ 30 kg/m²), lowering HbA_1c levels and improving lipid profiles. SGLT-2 inhibitors demonstrated greater efficacy in losing weight for patients with overweight (25 kg/m2 ≤ BMI < 30 kg/m2) and decreasing blood pressure.

Registration number: CRD42021247584. The name of the registry: PROSPERO. The URL to the registration: https://www.crd.york.ac.uk/PROSPERO/.

Objective: This study aims to develop and evaluate a dual-task deep learning framework for the simultaneous detection and classification of coronary lesions in invasive coronary angiography (ICA).

Materials and methods: A retrospective analysis was conducted using an annotated ICA dataset comprising 1234 patients (14,808 lesion-positive and 11,872 lesion-negative images), along with an external dataset of 135 cases. ICA video sequences were converted into 512 × 512 resolution images. A comprehensive preprocessing pipeline, including intensity normalization, noise suppression, and diverse data augmentation techniques (e.g., rotation, flipping, scaling, and brightness/contrast tuning), was applied to standardize image quality and enhance model generalizability. The proposed framework incorporates a detection module (utilizing YOLOv11, Swin Transformer, DETR, and Deformable DETR) and a classification module (featuring Vision Transformer (ViT), Swin Transformer, and ConvNeXt). The data were partitioned into training, validation, and testing subsets in an 80:10:10 ratio, and hyperparameter tuning was performed via grid search. Detection loss functions included Intersection over Union (IoU)-based losses, L1, and GIoU, while classification relied on weighted binary cross-entropy. Performance was evaluated using IoU, mAP, sensitivity, specificity, and AUC-PR.

Results: The detection module exhibited consistent high performance across both internal and external datasets. Deformable DETR achieved superior results on the external dataset, with a mAP of 88.2%, IoU of 87.0%, sensitivity of 92.0%, and specificity of 90.1%, outperforming other models. For classification, the Swin Transformer reached an external accuracy of 92.8%, AUC-PR of 0.94, and a Cohen's Kappa of approximately 0.89, exceeding the performance of ConvNeXt and ViT. These results are comparable to human expert performance in coronary lesion detection, where accuracy ranges from 85 to 90%, demonstrating the system's robust diagnostic capability. The achieved sensitivity and specificity values are clinically meaningful, as they reduce the risk of both false positives and false negatives, crucial for ensuring timely and accurate treatment decisions in clinical practice.

Conclusion: The proposed dual-task deep learning framework demonstrates a significant advancement in automated coronary lesion assessment by enabling accurate and efficient simultaneous detection and classification, thus supporting enhanced clinical decision-making.

Background: Although B vitamins are often consumed through multivitamin containing foods, their potential synergistic effects on cancer risk remain insufficiently elucidated.

Objective: We aimed to study the relationship between mixed intake of B vitamins, cancer, and overall and site-specific cancer risk in women.

Methods: A survey of dietary B vitamins intake and cancer risk was conducted using the National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2020.Generalized linear regression (GLM), weighted quantile, and regression (WQS) were used to evaluate the relationship between seven B vitamins intakes and cancer in the female population.

Results: A total of 17,495 adult women aged ≥ 20 years were included, with a mean age of 48.8 years and an average daily energy intake of 1,779 kcal. Dietary B-vitamin intake was obtained from two 24-h dietary recalls and reflected food-based (non-supplement) consumption. In the fully adjusted model, the mixed intake of seven B vitamins was inversely associated with overall cancer risk (adjusted OR = 0.91, 95% CI 0.85-0.98) and colorectal cancer (adjusted OR = 0.73, 95% CI 0.56-0.96). Folate, niacin, and choline contributed the greatest weights in the mixture model. In age-stratified analyses, the inverse association was present only in women younger than 65 years (adjusted OR = 0.86, 95% CI 0.79-0.94).

Conclusion: Synergistic intake of B vitamins demonstrates cancer-protective effects, with niacin and folate as primary contributors. These findings highlight the importance of consuming B vitamin-rich whole foods rather than from high-dose isolated supplements, particularly among younger women.

Background: Proliferative retinopathy (PR), a leading cause of visual impairment, is characterized by pathological retinal neovascularization. As an important methyltransferase, methyltransferase-like 14 (METTL14) plays a key role in the N6-methyladenosine (m⁶A) modification, which is the most widespread modification in mRNA and has been defined as a critical regulator in retinal diseases.

Methods: This study aims to clarify the mechanisms by which METTL14 regulates pathological retinal neovascularization in PR. The m⁶A levels were determined by m⁶A RNA colorimetric quantification in mice retinas and endothelial cells. The METTL14 levels in mice retinas and endothelial cells were detected by qPCR, western blotting and immunofluorescence assays. Retinal flat mounts from the oxygen-induced retinopathy (OIR) mice were used to assess the effects of METTL14 on retinal neovascularization. The effects of METTL14 on angiogenic functions of endothelial cells were measured by cell counting kit-8 (CCK-8), wound healing and tube formation assays. Mechanistically, we used the sequence-based RNA adenosine methylation site predictor (SRAMP) system to predict the target genes of METTL14 and performed qPCR, western blotting and RNA immunoprecipitation assays to validate their interactions. Statistical analyses were performed using Student's t test or one-way ANOVA.

Results: The levels of m⁶A and METTL14 were reduced in the retinas of OIR mice and in cobalt chloride (CoCl₂)-induced endothelial cells. METTL14 overexpression increased the m⁶A levels in mice retinas and endothelial cells. METTL14 overexpression in the OIR mice decreased the retinal neovascularization and vaso-obliteration. In CoCl₂-induced endothelial cells, METTL14 overexpression enhanced cells viability and reduced cells migration and tube formation. Mechanistically, METTL14 bound to hypoxia-inducible factor 1-alpha (HIF-1α) and suppressed HIF-1α levels.

Conclusions: This study suggests that METTL14-mediated m⁶A modification is a pivotal step in regulating the pathogenesis of retinal neovascularization. Therefore, METTL14 might be introduced as a promising therapeutic strategy for the management of PR. However, our findings are limited by the types of clinical samples, and further validation in larger clinical cohorts is required.

Background: Coronary heart disease (CHD) remains a leading global cause of morbidity and mortality. Dyslipidemia-particularly elevated non-high-density lipoprotein cholesterol (non-HDL-C) and reduced high-density lipoprotein cholesterol (HDL-C)-is a key risk factor for CHD. The ratio of non-HDL-C to HDL-C (NHHR) has been proposed as an integrative marker of lipid-related risk. We separately examined the cross-sectional association of NHHR with CHD status and its prospective association with long-term mortality in a nationally representative U.S.

Cohort:

Methods: We analyzed data from adults (aged ≥ 18 years) in NHANES 2005-2016. NHHR was calculated as non-HDL-C divided by HDL-C. Cross-sectional associations between NHHR and self-reported CHD were assessed using multivariable logistic regression. Prospective associations of baseline NHHR with all-cause and cardiovascular mortality were examined using Cox proportional hazards models. Restricted cubic splines (3 knots) were used to explore potential nonlinear relationships.

Results: Among ~ 20,000 adults, higher NHHR was paradoxically associated with lower odds of self-reported CHD. In fully adjusted models, participants in the highest NHHR quartile had an odds ratio of 0.39 (95% CI, 0.31-0.50; p < 0.0001) compared to the lowest quartile. In longitudinal analyses over a median follow-up of 7-10 years, higher NHHR was associated with lower hazard of all-cause and cardiovascular mortality. Spline analyses suggested a U-shaped relationship, with nadirs at NHHR ≈3.4 for all-cause and ≈3.3 for cardiovascular mortality (P for nonlinearity < 0.001).

Conclusions: In this large NHANES-based observational study, NHHR was cross-sectionally associated with lower CHD prevalence and longitudinally associated with reduced mortality. While similar patterns have been reported in prior NHANES studies, our analysis contributes additional insight by jointly modeling both CHD and mortality outcomes using nonlinear spline approaches and subgroup analyses. The paradoxical inverse association with CHD may reflect residual confounding or reverse causality. These findings remain exploratory and require cautious interpretation and further validation.

Purpose: This study aimed to investigate the distribution of epicardial adipose tissue (EAT) and adipose metabolism in patients with obstructive sleep apnea (OSA) without comorbidities, such as cardiovascular disease and diabetes-an approach to eliminate confounding factors and explore the role of EAT in OSA-related visceral adipose disorders.

Methods: The clinical data of 180 patients were retrospectively collected from July 2017 to December 2023 at the Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Xi'an Jiaotong University. Patients were categorized into mild-moderate (apnea-hypopnea index, AHI < 30 events/hour) and severe OSA groups (AHI ≥ 30 events/hour) based on their polysomnography (PSG) results. Epicardial adipose tissue volume (EATV) and attenuation (EATA) were quantified using coronary computed tomography angiography and 3D-Slicer software, with adipose tissue defined by a Hounsfield unit threshold of -190 to -30 HU. The Chinese visceral adiposity index (CVAI) is a composite metric specific to the Chinese population that integrates age, body mass index, waist circumference, triglyceride, and high-density lipoprotein levels.

Results: Significant differences were observed in EATV, EATA, and CVAI between the mild-moderate and severe OSA groups (all p < 0.05). Elastic net regression, restricted cubic spline curves, and subgroup analysis using forest plots demonstrated that CVAI had the strongest correlation with the apnea-hypopnea index (AHI) and OSA severity among the visceral adipose parameters (all p < 0.05). After controlling for the effects of baseline data and visceral adipose tissue, multiple linear regression analysis revealed that OSA severity still affected the EATV and EATA (all p < 0.05).

Conclusions: OSA progression without cardiovascular disease and diabetes may promote an increase in EATV, especially in the atrial region. In addition, the change in epicardial adipose tissue appears to be independent of visceral adipose tissue. This underscores EAT as a distinct fat depot and highlights its potential role in early cardiovascular risk assessment for OSA patients, offering perspectives for future research into mechanistic pathways and clinical interventions.

Objectives: To investigate and analyze the factors affecting postoperative urinary retention (POUR) after pelvic floor reconstruction, and to construct and validate a risk prediction model.

Methods: This retrospective cohort study included 258 pelvic floor reconstruction patients (2023-2024) from a Southwest China tertiary hospital. Patients were classified into POUR and non-POUR groups and split 7:3 into training and internal validation cohorts. Predictors were identified through univariate analysis and multivariate logistic regression analysis to construct a Nomogram model. Receiver Operating Characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow test evaluated the model's differentiation, calibration, goodness-of-fit, and predictive performance.

Results: Independent POUR risk factors were: urinary retention history (OR = 10.008, 95% CI 1.368-73.195, P = 0.023), heart disease (OR = 14.416, 95% CI 2.872-72.376, P = 0.001), number of vaginal deliveries (OR = 1.569, 95% CI 1.076-2.289, P = 0.019), and maximal urinary flow rate (OR = 0.845, 95% CI 0.76-0.94, P = 0.002). The AUC values of the training cohort and internal validation cohort were 0.812 (95% CI 0.726-0.899) and 0.822 (95% CI 0.703-0.941), respectively. Calibration curves indicated good agreement between predicted and observed values, and the Hosmer-Lemeshow test demonstrated high predictive accuracy (P > 0.05).

Conclusions: The nomogram model effectively predicts POUR risk, aiding early perioperative identification of high-risk patients.

Background: To assess the impact of oil overlay during maturation of immature oocytes in vitro in our optimized liquid culture system.

Methods: We conducted comparative analyses of pH, osmolality, and the levels of melatonin, FSH, E2, and hCG in the culture medium between oil-covered group (OC group) and non-oil-covered group (non-OC group). Furthermore, germinal vesicle (GV) oocytes were collected and matured into MII phase in our culture medium for 24 h. Subsequently, levels of ROS, SOD, MDA, and LDH were tested in OC group and non-OC group using either microplate assays or chemical fluorescence techniques. Finally, a total of 2432 immature oocytes obtained from controlled ovarian hyperstimulation (COH) cycles underwent in vitro maturation (IVM) in culture media with or without oil supplementation (1380 and 1052 oocytes, respectively), followed by insemination and embryo culture. The IVM prognostic indicators were assessed and compared between OC group and non-OC group.

Results: There were no statistically significant differences in pH and osmolality values between the OC group and the non-OC group. However, the concentrations of melatonin, FSH, E2, and hCG in non-OC group were significantly elevated in the non-OC group compared to the OC group. Regarding oxidative stress parameters, levels of ROS, MDA, and LDH in the culture medium of the non-OC group were lower than those in the OC group, while SOD levels were higher in the non-OC group. Furthermore, the clinical outcome assessments revealed significantly higher rates of maturation, cleavage, and blastocyst formation in the non-OC group compared to the OC group, with no discernible difference in fertilization rates between the two groups.

Conclusion: Omission of mineral oil overlay enhances hormone bioavailability, diminishes oxidative stress, and significantly improves oocyte maturation and blastocyst formation rates in IVM culture.